title: In vitro and in vivo immunostimulatory effects of hot water extracts from the leaves of Artemisia princeps Pampanini cv. Sajabal.
abstract: BACKGROUND
  Artemisia princeps Pampanini (Asteraceae) is used as a traditional medicine to immune function-related diseases, such as dysmenorrhea, inflammation, cancer, and ulcers.
  
  
  OBJECTIVE
  The purpose of this study is to evaluate the immunostimulatory effects of the hot water extract from the leaves of Artemisia princeps Pampanini (WAPP) in recombinant interferon-γ (rIFN-γ)-primed RAW 264.7 macrophages and in cyclophosphamide (20mg/kg, i.p.)-induced immunosuppressed Sprague-Dawley rats.
  
  
  METHODS
  RAW 264.7 macrophages were treated with WAPP and production and expressions of nitric oxide (NO) and tumor necrosis factor-α (TNF-α) via nuclear factor-κB (NF-κB) were detected by immunoassay, western blot, qRT-PCR and reporter gene assay. In addition, in vivo immunomodulatory activity was studied by cyclophosphamide-induced myelosuppression in rats.
  
  
  RESULTS
  In rIFN-γ-primed RAW 264.7 macrophages, pretreatment with WAPP increased the productions of nitric oxide (NO) and tumor necrosis factor-α (TNF-α),and increased the expressions of inducible nitric oxide synthase (iNOS) at the protein level and of iNOS and TNF-α at the mRNA level. Molecular data revealed that WAPP upregulated the transcriptional activity and translocation of nuclear factor-κB (NF-κB) by activating inhibitory kappa B-α (IκB-α) degradation and phosphorylation. Furthermore, WAPP upregulated the phosphorylations of p38 MAP kinase, c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase 1/2 (ERK1/2). In cycloheximide-induced immunosuppressed rats, pretreatment with WAPP (100, 200, or 400mg/kg, p.o.) increased the serum levels of albumin and globulin, and reduced immobility times.
  
  
  CONCLUSIONS
  Our results suggest that upregulations of the expressions of iNOS and TNF-α via the activations of NF-κB and MAPK are responsible for the immunostimulatory effects of WAPP.
authors.affiliation: Department of R&D, Chunho Food Co. Ltd., Busan, Republic of Korea.
authors.forename: Tae-Hee
authors.initials: TH
authors.lastname: Kim
authors.forename: Seung-Jun
authors.initials: SJ
authors.lastname: Lee
authors.forename: Hong-Kun
authors.initials: HK
authors.lastname: Rim
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Shin
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Jung
authors.forename: Jin-Sun
authors.initials: JS
authors.lastname: Heo
authors.forename: Jong-Bok
authors.initials: JB
authors.lastname: Kim
authors.forename: Myung-Suk
authors.initials: MS
authors.lastname: Lee
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
mesh_terms: D000276:Adjuvants, Immunologic / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D019306:Artemisia / Q000737:chemistry*; D018929:Cell Culture Techniques; D002460:Cell Line; D020834:Ethnopharmacology; D006358:Hot Temperature; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D055670:Medicine, Korean Traditional; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D056910:Republic of Korea; D013550:Swimming; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D014867:Water / Q000737:chemistry
chemical_list: D000276:Adjuvants, Immunologic; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D014867:Water; D009569:Nitric Oxide
keywords: Artemisia princeps Pampanini cv. Sajabal; Cyclophosphamide; ERK1/2; Immunostimulatory activity; IκB-α; JNK; NF-κB; NO; Nitric oxide; TNF-α; Tumor necrosis factor-α; WAPP; c-Jun NH2-terminal kinase; extracellular signal-regulated kinase1/2; hot water extract from the leaves of Artemisia princeps Pampanini; iNOS; inducible nitric oxide synthase; inhibitory kappa B-α; nitric oxide; nuclear factor-κB; qRT-PCR; quantitative reverse-transcriptase polymerase chain reaction; rIFN-γ; recombinant interferon-γ; tumor necrosis factor-α